HRP20040829A2 - Formulations of atorvastatin stabilized with alkali metal additions - Google Patents
Formulations of atorvastatin stabilized with alkali metal additionsInfo
- Publication number
- HRP20040829A2 HRP20040829A2 HR20040829A HRP20040829A HRP20040829A2 HR P20040829 A2 HRP20040829 A2 HR P20040829A2 HR 20040829 A HR20040829 A HR 20040829A HR P20040829 A HRP20040829 A HR P20040829A HR P20040829 A2 HRP20040829 A2 HR P20040829A2
- Authority
- HR
- Croatia
- Prior art keywords
- atorvastatin
- sodium
- alkali metal
- formulations
- carbonate
- Prior art date
Links
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 title abstract 8
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 title abstract 8
- 229960005370 atorvastatin Drugs 0.000 title abstract 8
- 238000009472 formulation Methods 0.000 title abstract 4
- 239000000203 mixture Substances 0.000 title abstract 4
- 229910052783 alkali metal Inorganic materials 0.000 title abstract 3
- 238000007792 addition Methods 0.000 title 1
- 150000001340 alkali metals Chemical class 0.000 title 1
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 abstract 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 abstract 3
- -1 alkali metal salt Chemical class 0.000 abstract 3
- 208000035150 Hypercholesterolemia Diseases 0.000 abstract 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 abstract 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 abstract 2
- 239000000654 additive Substances 0.000 abstract 2
- 230000000996 additive effect Effects 0.000 abstract 2
- 229910000019 calcium carbonate Inorganic materials 0.000 abstract 2
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 abstract 2
- 239000002245 particle Substances 0.000 abstract 2
- OJRHUICOVVSGSY-RXMQYKEDSA-N (2s)-2-chloro-3-methylbutan-1-ol Chemical compound CC(C)[C@H](Cl)CO OJRHUICOVVSGSY-RXMQYKEDSA-N 0.000 abstract 1
- XUKUURHRXDUEBC-SVBPBHIXSA-N (3s,5s)-7-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyheptanoic acid Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@H](O)C[C@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-SVBPBHIXSA-N 0.000 abstract 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 abstract 1
- 208000034599 Dysbetalipoproteinemia Diseases 0.000 abstract 1
- 201000010252 Hyperlipoproteinemia Type III Diseases 0.000 abstract 1
- 239000004115 Sodium Silicate Substances 0.000 abstract 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 abstract 1
- 206010060751 Type III hyperlipidaemia Diseases 0.000 abstract 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 abstract 1
- 229910052782 aluminium Inorganic materials 0.000 abstract 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 abstract 1
- RJZNFXWQRHAVBP-UHFFFAOYSA-I aluminum;magnesium;pentahydroxide Chemical compound [OH-].[OH-].[OH-].[OH-].[OH-].[Mg+2].[Al+3] RJZNFXWQRHAVBP-UHFFFAOYSA-I 0.000 abstract 1
- ANBBXQWFNXMHLD-UHFFFAOYSA-N aluminum;sodium;oxygen(2-) Chemical compound [O-2].[O-2].[Na+].[Al+3] ANBBXQWFNXMHLD-UHFFFAOYSA-N 0.000 abstract 1
- 229960001770 atorvastatin calcium Drugs 0.000 abstract 1
- 201000010099 disease Diseases 0.000 abstract 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 1
- 229910000397 disodium phosphate Inorganic materials 0.000 abstract 1
- 235000019800 disodium phosphate Nutrition 0.000 abstract 1
- 229910052742 iron Inorganic materials 0.000 abstract 1
- MZUOYVUQORIPHP-MNSAWQCASA-L magnesium;(3r,5r)-7-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyheptanoate Chemical compound [Mg+2].C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC([O-])=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1.C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC([O-])=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 MZUOYVUQORIPHP-MNSAWQCASA-L 0.000 abstract 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 abstract 1
- 235000019799 monosodium phosphate Nutrition 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 229910001388 sodium aluminate Inorganic materials 0.000 abstract 1
- 229910000029 sodium carbonate Inorganic materials 0.000 abstract 1
- 235000017550 sodium carbonate Nutrition 0.000 abstract 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 abstract 1
- 235000011121 sodium hydroxide Nutrition 0.000 abstract 1
- 229910000162 sodium phosphate Inorganic materials 0.000 abstract 1
- 239000001488 sodium phosphate Substances 0.000 abstract 1
- 235000011008 sodium phosphates Nutrition 0.000 abstract 1
- NTHWMYGWWRZVTN-UHFFFAOYSA-N sodium silicate Chemical compound [Na+].[Na+].[O-][Si]([O-])=O NTHWMYGWWRZVTN-UHFFFAOYSA-N 0.000 abstract 1
- 229910052911 sodium silicate Inorganic materials 0.000 abstract 1
- 235000019794 sodium silicate Nutrition 0.000 abstract 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 abstract 1
- 229910052725 zinc Inorganic materials 0.000 abstract 1
- 239000011701 zinc Substances 0.000 abstract 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/401—Proline; Derivatives thereof, e.g. captopril
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2009—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Inorganic Chemistry (AREA)
- Obesity (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Farmaceutska formulacija koja poboljšava biološkudostupnost i biološku ujednačenost, podrazumijevačestice amorfnog i/ili kristaličnog atorvastatina, čija veličina (d90) ne prelazi 150 µm, a prosječna veličina čestica (d50) varira unutar raspona od5-50 µm. Atorvastatin može biti kalcij atorvastatin, magnezij atorvastatin, aluminij atorvastatin, željezo atorvastatin, cink atorvastatin, ili njihova kombinacija. Formulacije atorvastatina mogu se stabilizirati miješanjem atorvastatina s aditivom soli alkalnog metala koji je u ukupnoj težini formulacije zastupljen s 1.2% do manje od 5%. Aditiv soli alkalnog metala može biti natrijev karbonat, natrijev bikarbonat, natrijev hidroksid, natrijev silikat, dinatrij hidrogen ortofosfat, natrijev dihidrogen fosfat, dinatrijev hidrogen fosfat, natrijev fosfat, natrijev aluminat, kalcijev karbonat, kalcijev hidroksid, magnezijev karbonat, magnezijevhidroksid, magnezijev silikat, magnezijev aluminat, aluminij magnezijev hidroksid, odnosno jedna odnjihovih kombinacija. Formulacije atorvastatina koriste se u liječenju bolesti kao što je primarna hiperkolesterolemija, disbetalipoproteinemija te homozigotična familijama hiperkolesterolemija.A pharmaceutical formulation that improves bioavailability and biological uniformity comprises amorphous and / or crystalline atorvastatin particles, whose size (d90) does not exceed 150 µm, and the average particle size (d50) varies within the range of 5-50 (m. Atorvastatin may be atorvastatin calcium, atorvastatin magnesium, atorvastatin aluminum, atorvastatin iron, atorvastatin zinc, or a combination thereof. Atorvastatin formulations can be stabilized by mixing atorvastatin with an alkali metal salt additive which is present in the total weight of the formulation from 1.2% to less than 5%. The alkali metal salt additive may be sodium carbonate, sodium bicarbonate, sodium hydroxide, sodium silicate, disodium hydrogen orthophosphate, sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium phosphate, sodium aluminate, calcium carbonate, carbonate, calcium carbonate, calcium magnesium aluminate, aluminum magnesium hydroxide, or one of their combinations. Atorvastatin formulations are used in the treatment of diseases such as primary hypercholesterolemia, dysbetalipoproteinemia, and homozygous families of hypercholesterolemia.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IN112DE2002 | 2002-02-14 | ||
PCT/IB2003/000505 WO2003068191A1 (en) | 2002-02-14 | 2003-02-14 | Formulations of atorvastatin stabilized with alkali metal additions |
Publications (1)
Publication Number | Publication Date |
---|---|
HRP20040829A2 true HRP20040829A2 (en) | 2006-07-31 |
Family
ID=27620520
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HR20040829A HRP20040829A2 (en) | 2002-02-14 | 2004-09-13 | Formulations of atorvastatin stabilized with alkali metal additions |
Country Status (23)
Country | Link |
---|---|
US (1) | US20030175338A1 (en) |
EP (1) | EP1336405A1 (en) |
JP (1) | JP2005522444A (en) |
KR (1) | KR20040101229A (en) |
CN (1) | CN1642526A (en) |
AP (1) | AP2004003112A0 (en) |
AR (1) | AR038839A1 (en) |
AU (1) | AU2003245736A1 (en) |
BR (1) | BR0307720A (en) |
CA (1) | CA2475722A1 (en) |
CO (1) | CO5600997A2 (en) |
EA (1) | EA200401059A1 (en) |
EC (1) | ECSP045235A (en) |
HR (1) | HRP20040829A2 (en) |
IL (1) | IL163550A0 (en) |
IS (1) | IS7404A (en) |
MX (1) | MXPA04007905A (en) |
NO (1) | NO20043790L (en) |
OA (1) | OA12777A (en) |
PE (1) | PE20030935A1 (en) |
PL (1) | PL371337A1 (en) |
WO (1) | WO2003068191A1 (en) |
ZA (1) | ZA200406970B (en) |
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WO2002057229A1 (en) | 2001-01-19 | 2002-07-25 | Biocon India Limited | FORM V CRYSTALLINE [R-(R*,R*)]-2-(4-FLUOROPHENYL)-ß,$G(D)-DIHYDROXY-5-(1-METHYLETHYL)-3-PHENYL-4-[(PHENYLAMINO)CARBONYL]-1H-PYRROLE-1- HEPTANOIC ACID HEMI CALCIUM SALT. (ATORVASTATIN) |
US7361772B2 (en) * | 2001-08-16 | 2008-04-22 | Biocon Limited | Process for the production of atorvastatin calcium |
ATE452871T1 (en) | 2002-03-18 | 2010-01-15 | Biocon Ltd | AMORPHOUS HMG-COA REDUCTASE INHIBITORS WITH DESIRED PARTICLE SIZE |
US7179942B2 (en) | 2002-07-05 | 2007-02-20 | Bicon Limited | Halo-substituted active methylene compounds |
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US20050271717A1 (en) * | 2003-06-12 | 2005-12-08 | Alfred Berchielli | Pharmaceutical compositions of atorvastatin |
EP1653930B1 (en) * | 2003-08-05 | 2007-12-19 | Zentiva, a.s. | Methods for the stabilization of atorvastatin |
AU2003272080A1 (en) | 2003-09-18 | 2005-04-06 | Biocon Limited | Novel process for the preparation of tert-butyl 6-cyano-5-hydroxy-3-oxohexanoate |
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WO2007053904A1 (en) | 2005-11-10 | 2007-05-18 | Alphapharm Pty Ltd | Process to control particle size |
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CN104069502B (en) * | 2013-03-29 | 2018-02-16 | 北京罗诺强施医药技术研发中心有限公司 | Compound skeleton material and its pharmaceutical composition |
JP6507808B2 (en) * | 2015-04-09 | 2019-05-08 | ニプロ株式会社 | Oral disintegrating tablet |
WO2017106130A1 (en) * | 2015-12-16 | 2017-06-22 | Merck Sharp & Dohme Corp. | Process for preparing pharmaceutical compositions |
EP3184103A1 (en) | 2015-12-21 | 2017-06-28 | Hexal AG | Pharmaceutical composition comprising atorvastatin or a salt thereof |
CN106420645A (en) * | 2016-11-24 | 2017-02-22 | 浙江新东港药业股份有限公司 | Calcium tablet containing atorvastatin and preparation method |
CN108421045B (en) * | 2018-04-02 | 2021-09-24 | 北京海晶生物医药科技有限公司 | Atorvastatin calcium composition, preparation and preparation method thereof |
CN109044989A (en) * | 2018-10-09 | 2018-12-21 | 河南师范大学 | A kind of atorvastatin calcium capsule preparation and preparation method thereof |
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HU9203780D0 (en) * | 1991-12-12 | 1993-03-29 | Sandoz Ag | Stabilized pharmaceutical products of hmg-coa reductase inhibitor and method for producing them |
WO1994016693A1 (en) * | 1993-01-19 | 1994-08-04 | Warner-Lambert Company | Stable oral ci-981 formulation and process of preparing same |
SI20109A (en) * | 1998-12-16 | 2000-06-30 | LEK, tovarna farmacevtskih in kemi�nih izdelkov, d.d. | Stable pharmaceutical formulation |
US6242003B1 (en) * | 2000-04-13 | 2001-06-05 | Novartis Ag | Organic compounds |
SI20848A (en) * | 2001-03-14 | 2002-10-31 | Lek, Tovarna Farmacevtskih In Kemijskih Izdelkov, D.D. | Pharmaceutical formulation containing atorvastatin calcium |
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2003
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ZA200406970B (en) | 2005-06-20 |
IL163550A0 (en) | 2005-12-18 |
PL371337A1 (en) | 2005-06-13 |
CA2475722A1 (en) | 2003-08-21 |
OA12777A (en) | 2006-07-06 |
EP1336405A1 (en) | 2003-08-20 |
NO20043790L (en) | 2004-11-08 |
PE20030935A1 (en) | 2003-10-30 |
AP2004003112A0 (en) | 2004-09-30 |
ECSP045235A (en) | 2004-09-28 |
US20030175338A1 (en) | 2003-09-18 |
WO2003068191A1 (en) | 2003-08-21 |
CO5600997A2 (en) | 2006-01-31 |
EA200401059A1 (en) | 2005-02-24 |
AR038839A1 (en) | 2005-01-26 |
BR0307720A (en) | 2005-01-25 |
AU2003245736A1 (en) | 2003-09-04 |
MXPA04007905A (en) | 2004-11-26 |
JP2005522444A (en) | 2005-07-28 |
KR20040101229A (en) | 2004-12-02 |
CN1642526A (en) | 2005-07-20 |
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